Antimicrobial susceptibility test (AST) methods have certainly moved into many directions from the standard disk diffusion method over the decades. One of the first disk publications about the methodology was by Howe in 1950 and later Borchardt and Andrew in 1959. However, the method was standardized by Bauer and Kirby and colleagues in 1966, followed by further refinements by Clyde Thornsberry at the CDC, and also L. Thrupp, from the 1970s. Besides broth macro or micro-dilution, Kirby Bauer disk diffusion is also considered a reference method and is well accepted in clinical microbiology laboratories due to the ease of use.
|Drs. Kirby and Bauer, 1966|
Disk diffusion is especially preferred over minimum inhibitory concentration methods when applied to new antimicrobial agents being introduced to clinical laboratories, as the disk is normally the first FDA-cleared device.
Through coordinated development efforts since early 2016 between pharmaceutical companies, the FDA, and AST device manufacturers AST devices have been developed in parallel during the antimicrobial clinical trials to allow for the antimicrobial and AST devices to be FDA cleared as closely together as possible. This allows for labs to quickly validate the AST devices and implement the antimicrobial in patient treatment soon after the antimicrobial receives drug clearance.
This quick turn-around time from drug approval to market clearance of the AST devices allows hospitals to adopt new antimicrobials more quickly by providing labs a simple way of testing the susceptibility of bacteria from patient specimens.
Additionally, the disk diffusion method is easy to use with little equipment required and is low in cost. In 2018, three new antimicrobials entered the market: Plazomicin (an aminoglycoside) by Achaogen, Eravacycline (a new tetracycline) by Tetraphase, and Omadacycline (another new tetracycline) by Paratek. Plazomicin and Eravacycline disks (HardyDisk™ AST) were FDA-cleared in record-breaking time after drug approval. This trend continued from the steady stream of new antimicrobials that became commercially available in 2017: Meropenem/Vaborbactam (beta-lactam combination drug) by The Medicines Company and Delafloxacin (a new fluoroquinolone) by Melinta. Once again, the HardyDisks for these two antimicrobials in 2017 were also cleared rapidly in comparison to prior years of drug development.
The steady release of new antimicrobials
to the clinical market is encouraging for the continued growth and development of AST methods and technologies, as well as identifying treatments for particular antibiotic resistant organisms.
With the continuation of coordinated development between all groups involved in antimicrobial agents and AST methods, Kirby Bauer disk diffusion is here to stay. Although there are some compounds for which disk diffusion is not intended (e.g. colistin), the ability to test organisms in a cost-effective and simple method has allowed for the continuous introduction of new antimicrobial agents that can be implemented in clinical microbiology labs within the same year as drug approval.
While other automated AST systems or the gradient systems are able to deliver MICs, the addition of newly approved antibiotics into these systems may be more time-consuming.
Without a doubt, Kirby Bauer disk diffusion remains the gold standard and the best way to implement new antimicrobials quickly into the work-flow of microbiology laboratories, and thus, leads to better patient treatment outcomes.
Submitted by Anna Klavins, Rianna Malherbe and Andre Hsiung
Technical Services Department
With special gratitude to Dr. Stephen Jenkins from Cornell University Medical Center who helped with the historical perspective and references.
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